Oral monotherapy for major depressive disorder entering phase 3 trials
‘Trial and error’ treatment approach for major depressive disorder has pros and cons, experts say
A phase 3 clinical program has been initiated for a potential monotherapy for the treatment of major depressive disorder (MDD).
The monotherapy treatment is navacaprant (NMRA-140), an oral, once-daily, 80 mg, novel kappa opioid receptor (KOR) antagonist designed to modulate the dopamine and reward processing pathways. Navacaprant showed statistically significant and clinically meaningful reductions in symptoms of anhedonia and depression among patients with moderate to severe MDD in its phase 2 studies.1
Following a positive end-of-phase 2 meeting between navacaprant developer Neumora Therapeutics and the US Food & Drug Administration (FDA) in June 2023, navacaprant has been approved for study in the KOASTAL Program, a phase 3 pivotal clinical program that will further evaluate the safety and efficacy of the drug.1
The KOASTAL Program will consist of KOASTAL-1, KOASTAL-2, and KOASTAL-3—3 randomized, placebo-controlled, double-blind studies that will assess navacaprant monotherapy in adult patients with moderate to severe MDD who have a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥ 25 at baseline. The primary endpoint for each study will be a change from baseline MADRS total score at week 6. The key secondary endpoints will be a change from baseline on the Snaith-Hamilton Pleasure Scale (SHAPS) at week 6.1
The KOASTAL-1, KOASTAL-2, and KOASTAL-3 studies will be initiated in the third quarter of 2023, the fourth quarter of 2023, and the first quarter of 2024, respectively.1
“The planned initiation of the KOASTAL program represents an important step toward our goal of bringing a truly novel treatment to people living with MDD,” said Paul L. Berns, co-founder and executive chairman of Neumora, in a press release. “The data from our phase 2 study with navacaprant demonstrate its potential as a differentiated antidepressant that may help to manage anhedonia in addition to other core symptoms of depression with a favorable safety profile.”
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